International Journal of Clinical and Experimental Pathology
·
2015
·
IF 1.891
Qingwei Zhang,Haiya Wu,Congcong Wen,Fa Sun,Xuezhi Yang,Lufeng Hu
MGCD0103, an isotype-selective HDACi, has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In this study, we developed a serum metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of intragastric administration of MGCD0103 on rats. The MGCD0103 group rats were given 20, 40, 80 mg/kg of MGCD0103 by intragastric administration each day for 7 days. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) revealed that intragastric administration of MGCD0103 induced metabolic perturbations. As compared to the control group, the levels of L-alanine, L-isoleucine, and L-leucine of MGCD0103 group decreased. The results indicate that metabolomic methods based on GC-MS may be useful to elucidate side effect of MGCD0103 through the exploration of biomarkers (L-alanine, L-isoleucine, and L-leucine). According to the pathological changes of liver at difference dosage, MGCD0103 is hepatotoxic and its toxity is dose-dependent.
研究领域:
药理学
·
代谢组学
·
毒理学
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2020
·
IF 2.369
Shengzheng Guo,Yang He,Gang Wang,Weibing Dong,Xuxing Wan,Yanxiao Zhao,Shichao Du
The solubility of N-acetyl-l-leucine in 12 mono organic solvents (methanol, ethanol, n-propanol, 2-propanol, 1-butanol, isobutanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, acetone, and acetonitrile) was determined by the gravimetric method over the temperatures ranging from 283.15 to 323.15 K at 0.1 MPa. The solubility of N-acetyl-l-leucine in each experimental solvent increases with increasing temperature. Moreover, the solubility is an order of magnitude higher in alcohol solvents than in other solvents, which is mainly attributed to the hydrogen bond formation. In addition, the experimental solubility data are correlated by three models, including the modified Apelblat equation, λh equation, and the nonrandom two-liquid (NRTL) model. All of the average relative deviation % values are less than 3.72%, which indicates that the three models have satisfactory correlations. Furthermore, the mixing thermodynamic properties of N-acetyl-l-leucine in 12 mono solvents including ΔmixG0, ΔmixH0, and ΔmixS0 are calculated based on the NRTL model, indicating that the mixing process was spontaneous.
研究领域:
物理化学
·
药物化学
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产品关联
DOI
高影响因子
MICROBIOLOGICAL RESEARCH
·
2024
·
IF 6.1
Lingyun Zhang,Xuelei Deng,Jia Xiao,Wei Zhao,Pan Zou,Ruizhe Liao,Keying Xie,Hongdong Liao
The recruitment of the phosphorus-solubilizing rhizobacteria plays an important role in response to phosphorus deficiency. Through the treatments of Arabidopsis thaliana (Col-0) and the FERONIA (FER) functional deficient mutants ( fer-4 and fer-5 ) with the soil suspension in various phosphorus conditions, we discovered that FER could promote phosphorus-solubilizing rhizobacteria enrichment to rescue the defective plant during phosphorus deficiency. The amplicon sequencing data reflected that the phosphorus-solubilizing rhizobacterial genus Alcaligenes was significantly enriched of Col-0 than fer-4 in low phosphorus conditions. Metabolomics analysis revealed that there were more α-D-Glucose (α-D-Glc) and L-Leucine (L-Leu) in Col-0 roots than those in fer-4 roots. The alterations of α-D-Glc and L-Leu mediated by FER had high-positive correlations to the enrichment of Alcaligenes . We successfully isolated a phosphorus-solubilizing rhizobacteria strain identified as Alcaligenes faecalis PSB15. The α-D-Glc and L-Leu could promote the strain PSB15 growth on LB agar plates and assist fer-4 in recovering from phosphorus starvation in the low phosphorus (LP) liquid medium vermiculite with tricalcium phosphate (TCP). The α-D-Glc and L-Leu could be considered as promising compounds to enrich beneficial phosphorus-solubilizing rhizobacteria, such as Alcaligenes , and provide a reference for overcoming the plight of phosphorus deficiency in crops in the field of agricultural production in the future.
研究领域:
植物科学
·
微生物学
·
土壤科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 67
·35597-35608
·
IF 3.708
Dufen Hu,Baoyang Lu,Xuemin Duan,Jingkun Xu,Long Zhang,Kaixin Zhang,Shimin Zhang,Shijie Zhen
Two amino acid-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives, poly(N-(tert-butoxycarbonyl)-L-leucyl(3,4-ethylenedioxythiophene-2′-yl)methylamide) (PEDOT–Boc–Leu) and poly(L-leucyl(3,4-ethylenedioxythiophene-2′-yl)methylamide) (PEDOT–Leu) were synthesized electrochemically via potentiostatic polymerization of corresponding monomers N-(tert-butoxycarbonyl)L-leucyl(3,4-ethylenedioxythiophene-2′-yl)methylamide (EDOT–Boc–Leu) and L-leucyl(3,4-ethylenedioxythiophene-2′-yl)methylamide (EDOT–Leu), which were synthesized by grafting Boc-L-leucine and L-leucine into a 3,4-ethylenedioxythiophene (EDOT) side chain. The electrochemical behaviors, structural characterization, circular dichroism, spectroscopic properties, surface morphology, electrochromic properties and thermal stabilities of PEDOT–Boc–Leu and PEDOT–Leu films were systematically investigated. These L-leucine grafted PEDOT derivatives displayed excellent reversible redox activities, rough and compact surface, and good thermal stability. The circular dichroism spectra suggested the chirality of these polymers. Importantly, the introduction of the L-leucine group enhanced the electrochromic properties of PEDOT and resulted in high contrast ratios (ΔT% = 49% at 600 nm for PEDOT–Boc–Leu) and high coloration efficiencies (431 cm2 C−1 at 960 nm for PEDOT–Leu). Satisfactory results implied that the obtained polymer films can probably be further developed in various applications, such as electrochromic devices, optical displays and chiral recognition.
研究领域:
材料科学
·
电化学
·
光学材料
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Xuejuan Zhang,Yue Zhou,Guanlin Wang,Ziyu Zhao,Zhongxiang Jiang,Yingtong Cui,Xiao Yue,Zhengwei Huang,Ying Huang,Xin Pan,Chuanbin Wu
Poly-L-lysine (PLL) is a promising candidate for the treatment of pulmonary infection with lower occurrence of drug-resistance due to its unique antibacterial mechanisms. Dry powder inhalations (DPIs) are considered as the first choice for formulating PLL to treat pulmonary infection on account of direct delivery and satisfactory stability. However, hygroscopicity of PLL limited its therapeutic effect on pulmonary infection when PLL developed into DPIs. The hygroscopicity caused two obstacles including the low drug deposition in the lower respiratory tract and undesirable aerosolization performance deterioration. In this study, PLL was co-spray-dried with L-leucine (LL) to achieve moisture-resistance and desirable aerosolization performance. The ratio of PLL and LL was optimized to obtain particles with different morphology, hygroscopicity and aerodynamic properties. The obtained PLL DPIs were suitable for inhalation with a corrugated surface formed by hydrophobic LL. The anti-hygroscopicity, aerosolization performance and rheological properties of P 2 DPIs were optimal when PLL:LL = 85:15. The DPIs particles were stable after being stored at high relative humidity (60 ± 5%), and their superiority in treating pulmonary infections was also proved by in vitro and in vivo experiments. The established PLL DPIs were proved to be a feasible and desirable approach to treat pulmonary infections.
研究领域:
药学
·
呼吸医学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 3
·1-12
·
IF 3.3
Zhang Qian,Li Yongquan,Li Linghui,Cheng Yushan,Yu Fangkun,Li Rui,Hou Shuguang
Amorphous and crystalline active pharmaceutical ingredients (APIs) are both widely studied for pulmonary delivery. The past research mainly studied the impact of solid-state properties on pharmacokinetic attributes; however, the influence of solid-state properties on aerosolization performance was much less studied. This study aimed to investigate the different aerosolization performances of amorphous and crystalline curcumin (Cur) stabilized with L-leucine. Cur was spray-dried with different concentrations of L-leucine (0, 5, 20, 35, and 50%, w/w) as both solution-based and suspension-based formulations to acquire amorphous and crystalline Cur powders. The physicochemical properties of the spray-dried powders, including particle size, morphology, and solid-state characteristics, were studied. The aerosolization performance as well as dissolution properties were evaluated. It was found that 35% (w/w) L-leucine or above led to the formation of amorphous Cur in the spray-dried powders, and the amorphous Cur powders exhibited higher FPF (70.8%, with 50% L-leucine, w/w) than the crystalline Cur formulations with an FPF at 56.3% (with 50% L-leucine, w/w). In conclusion, with a high concentration of L-leucine (35% or above) in the formulations, amorphous Cur would exhibit higher aerosolization efficiency than crystalline Cur. However, with a low concentration of L-leucine (20% or less) in the formulations, crystalline Cur would be preferred for more enhanced consideration. Graphical Abstract
研究领域:
药学
·
肺科学
·
制剂科学
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产品关联
DOI
PubMed
高影响因子
FOOD AND BIOPRODUCTS PROCESSING
·
2023
·
IF 4.6
Yulu Du,Yue Wang,Tianyou Cui,Lianpeng Ge,Fan Yu,Mengqian Zhao,Qihang Xu,Mingjie Jin,Bo Chen,Xuwei Long
Biosurfactant surfactin has a high market value and broad application prospects in the food industry and various industrial fields. However, its production efficiency limits its suitability for real applications. In this study, a new Bacillus subtilis (sp.) 50499 strain was isolated from crude oil-contaminated soil and used to efficiently produce surfactin. The initial surfactin titer was 2.25 g/L after three days of fermentation. Adding 2 g/L of L -Leu significantly improved the titer to over 5.5 g/L after optimizing the culture medium at 37 °C. However, adding D -Leu had the opposite effect on surfactin production , and the surfactin titer dropped to below 0.2 g/L. Furthermore, the product of this strain was analyzed to confirm the identity of surfactin. The surfactin obtained in the present study reduced the surface tension of water to 28.6 mN/m at a critical micelle concentration of 20 mg/L. The emulsification index against n -hexane, corn , and crude oil was as high as over 90%. Hence, the present study provides a newly over-producing strain for surfactin production.
研究领域:
微生物学
·
生物技术
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产品关联
DOI
高影响因子
CHROMATOGRAPHIA
·
2023
·Vol. 86
·期 7
·541-551
·
IF 1.7
Guo Xinyuan,Shang Panpan,Wei Benben,Du Wenrong,Lan Yong,Bai Ligai,Qiao Xiaoqiang,Ma Zhengyue
This study presents the development of three new chiral stationary phases. Three new peptide chiral stationary phases with a main chain of l- proline, l- phenylalanine, l- valine and l- leucine and different terminals of l- citrulline, l- lysine and l- tryptophan immobilized on 3-aminopropyltrimethoxysilane modified silica gel were prepared; furthermore, successful analyses and characterizations were conducted using Fourier transform infrared spectra, elemental analysis, and thermogravimetric analysis. After this, the enantioselective performance of the three peptide stationary phases columns was evaluated. The evaluation used nine racemic compounds under normal-phase high-performance liquid chromatography mode. Optimized enantiomeric separation conditions were established. Under these conditions, the resolutions of flurbiprofen, naproxen, benzoin, 1 ,1ʹ-bi-2-naphthol and ketoprofen on the CSP-1 column were 1.61, 2.0, 0.62, 0.52 and 1.20, respectively. In addition, the reproducibility of the CSP-1 column was also investigated. The results of the investigation illustrated that the stationary phases have good reproducibility (RSD = 0.12%, n = 5).
研究领域:
分析化学
·
色谱学
·
材料科学
·
分离科学
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DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2021
·Vol. 56
·期 12
·7626-7636
·
IF 4.22
Xie Yan-Yan,Qin Xiao-Tong,Feng Jia-Yuan,Zhong Cheng,Jia Shi-Ru
Abstract Amino acid-based hydrogels with broad-spectrum antibacterial properties are increasingly popular alternatives to existing treatments in the fight against bacterial infection. Here, an amino acid-based hydrogel formed by the self-assembly of N -(9-fluorenylmethoxycarbonyl)- L -Leucine (Fmoc-L) and Fmoc- L -Lysine (Fmoc-K) is reported. The Fmoc-L/Fmoc-K hydrogel, which consisted of twisted nanobelts, displayed antibacterial activity against Gram-positive S. aureus , B. subtilis , L. monocytogenes , and Gram-negative E. coli , Sh. sonnei . Specifically, inhibition rates of 97%, 100%, 44%, 45%, and 32% were achieved against S. aureus , B. subtilis , L. monocytogenes , E. coli , and Sh. sonnei after incubation with 4 mM of an Fmoc-L/Fmoc-K hydrogel with the molar ratio of 3:1 for 2 h, respectively. The inhibition rates against E. coli and Sh. sonnei reached 80% and 55% after treatment with 10 mM hydrogel, respectively. The antibacterial activity of hydrogels was time-dependent and enhanced with the prolongation of time. Additionally, the antibacterial activity was easily tailored by modifying the molar ratio of Fmoc-L and Fmoc-K. It was found that Fmoc-L/Fmoc-K hydrogel targeted and destroyed the bacterial cell membrane, causing cytoplasmic leakage and eventually cell death. Moreover, the hydrogel also displayed antibacterial action by inducing the agglomeration of S. aureus . This work demonstrates the potential of amino acid-based hydrogels as a new class of effective antibacterial materials in biomedical applications. Graphical abstract A
novel amino acid-based hydrogel formed by the self-assembly of Fmoc-L leucine and
Fmoc-L lysine , which consisted of twisted nanobelts, displayed antibacterial activity
against Gram-positive and Gram-negative bacteria.
研究领域:
材料科学
·
生物医学工程
·
微生物学
·
纳米技术
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
·
分子生物学
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Luyao Zheng,Zhiyuan Zhao,Ye Yang,Yaming Li,Chengxiao Wang
This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility . In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs).
研究领域:
药学
·
药物递送系统
·
药剂学
·
材料科学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Pei Liu,Xiao-ying Tan,Huang-qin Zhang,Ke-lei Su,Er-xin Shang,Qing-ling Xiao,Sheng Guo,Jin-ao Duan
Ethnopharmacological relevance The herbal pair of Trichosanthis Pericarpium (TP) - Trichosanthis Radix (TR) can be seen in the famous formula “Beimu Gualou San”. It is a commonly selected combination of medicinal herbs for the treatment of cough with lung heat. Both drugs are derived from Trichosanthes kirilowii Maxim, a medicinal plant known for its ability to clear heat, resolve phlegm, produce saliva, and alleviate dryness. However, the optimal combination ratio and active ingredients of TP-TR have yet to be determined. Aim of the study This study aims to investigate the optimal combination ratio of TP-TR and its anti-inflammatory active ingredients in cough treatment. Materials and methods A zebrafish ( Danio rerio ) inflammatory injury model and response surface method were applied in the present study to determine the appropriate proportion of TP-TR. Chemical constituents in TP-TR were identified using HPLC-ELSD and UPLC-MS/MS methods. Subsequently, a cough mouse model was created using an ammonia solution to evaluate the effectiveness of the optimal TP-TR ratio. Network pharmacology and intestinal flora sequencing were used to validate the anti-inflammatory components of TP-TR. Results The herbal pair of TP - TR at the ratio of 1:2 showed an optimal anti-inflammatory effect, with a composite inflammatory factor score of 119.645 in the zebrafish experiment. TP-TR combination facilitated the dissolution of glutamine, inosine , cytosine , isoquercetin , and other substances. In the animal model, the TP-TR (1:2) treatment significantly reduced the frequency of coughs and prolonged cough latency compared to the model group. Results of the network pharmacology indicated that inflammatory-related factors such as TLR4 , STAT3, EGFR, and AKT1 played crucial roles in cough treatment with TP-TR, consistent with the validation experiment. The 16s rDNA sequencing results revealed a significant increase in the abundance of Clostridia_UCG-014, Lachnospiraceae , Christenella, Ruminococcus , and other species in the intestinal tract of mice after modelling. TP-TR (1:2) reduced the abundance of pro-inflammatory flora such as Clostridium_UCG-014 and Lachnospira , which were closely associated with L-lysine and trans-4-hydroxy-L-proline present in TP-TR according to correlation analysis. Conclusion TP-TR may promote the dissolution of glutamine, thymidine , inosine, cytosine, isoquercetin, and other components through their combination, thereby regulating the abundance of Clostridium_UCG-014 and Lachnospira and exerting an antitussive effect. This study, for the first time, showed that TP-TR at a 1:2 ratio exhibits superior anti-inflammatory effects. In addition to inflammatory mediators like EGFR, TLR4, AKT1, and STAT3, gut microbes could also serve as potential regulatory targets of TP-TR in the treatment of cough. 2'-Deoxyguanosine monohydrate, L-lysine, L-leucine, γ-aminobutyric acid, L-valine, L-tryptophan, L-proline, trans-4-hydroxy-L-proline, L-methionine, uridine , 2'-deoxyinosine, guanosine , cucurbitacin B and cucurbitacin D were identified as its anti-inflammatory active ingredients.
研究领域:
药理学
·
民族药理学
·
炎症
·
中药
·
动物模型
·
网络药理学
·
微生物组
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）